Individual Case Safety Reports (ICSRs) - AFMPS - Case... · 8 FAMHP/mtg 15.05.2012 Federal Agency...

Federal Agency for Medecines and Health Products

Federal Agency for Medicines and Health Products

(FAMHP)

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15.05.2015

Pharm. Margriet Gabriëls, PhD

DG Post, Vigilance

Individual Case Safety Reports (ICSRs) :

new definition of adverse reaction

reporting rulesand others

BRAS 15.05.2015

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Content of the Presentation

1. New ADR definitions• Adverse reaction

• Overdose – Misuse – abuse – medication error – occupational exposure

2. Reporting Rules : ‘key changes’

3. Good Vigilance Practice : Module VI : Management and reportingof adverse reactions to medicinal Products (Draft Document)

4. Standard & Format of Pharmacovigilance information : “International Standardisation”

1. Medicinal Products

2. ICSRs

5. Data Access Policy

6. Data Quality Management

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New definition of Adverse Reaction (Regulation 1235/2010 Art. 1)

‘a response to a medicinal product which is noxious and unintended’

The directive 2010/84/EU removed the reference to the normaldose since “the term ‘adverse reaction’ should (…) ensure that itcovers noxious and unintended effects resulting not only fromthe authorised use of a medicinal product at normal doses, butalso from medication errors and uses outside the terms of the marketing authorisation, including the misuse and abuse of a medicinal product” (Recital 5)

This includes also reporting of ADRs not only in normal conditions of use, but also from :

- uses outside terms of Marketing Authorisation : misuse and abuse

- medication error

- overdose

- occupational exposure

No No definitionsdefinitions in the in the legislationlegislation but …..

New definitions in pharmacovigilance legislation (I)

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GVP (draft document) defines the following terms : a. OverdoseThis refers to the administration of a quantity of a medicinal product given per administration or per day, which is above the maximal recommended doseaccording to the authorised product information. This shall also take into account cumulative effects due to overdose.

b. MisuseThis refers to situations where the medicinal product is intentionally and inappropriately used not in accordance with the prescribed or authorised dose, route of administration, and/or the indication(s) or within the legal status of its supply (e.g. without prescription for medicinal products subjects to medical prescription).

c. AbuseAs defined in Article 1 of Directive 2001/83/EC, this relates to the sporadic or persistent, intentional excessive use of a medicinal product, which is accompanied by harmful physical or psychological effects.

d. Medication errorThis refers to any unintentional error in the prescribing, dispensing or administration of a medicinal product while in the control of the healthcare professional, patient or consumer.

e. Occupational exposureThis corresponds to the exposure to a medicinal product for human use as a result of one’s occupation.

New definitions in pharmacovigilance legislation (II)

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Aim of changing reporting rules :

Better data collection:

- Expedited requirements for non-serious reports

- Patient reporting

- Literature monitoring by EMA

- Medication errors that result in ADRs are collected

Simplified logistics for reporting (after transitional period) :

- All ADRs from MAHs and MSs sent to EV only

- MSs are ‘auto-forwarded’ their national data

- MAHs access reports in EudraVigilance (EV)

Reporting Rules : Key changes (I)

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After transitional period :

Serious/non-serious ADRs should be expeditedly reported :

MAHs shall submit:

•Information on all serious suspected adverse reactions that occur in the EU and in 3rd countries within 15 days

•Non-serious suspected adverse reactions that occur in the EU within 90 days

•‘Expectedness’ is no longer relevant

•Expedited reporting of non-serious ADRs only for reports originating from EU (3rd countries under discussion)

To Day : as is!All ICSRs, reportable to FAMHP, should be sent to the EMA’sEudravigilance Database

http://www.fagg-afmps.be/nl/news/news_eudravigilance_avril_2011.jsphttp://www.fagg-afmps.be/fr/news/news_eudravigilance_avril_2011.jsphttp://www.fagg-afmps.be/en/news/news_eudravigilance_avril_2011.jsp

Reporting Rules : Key changes (II)

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HCP & patient reports requested :

The MAH shall record all suspected adverse reactions in the EU or

in 3rd countries, whether reported spontaneously by patients or HCPs, or occurring in the context of a post-authorisation study

The MAH shall not refuse to consider reports of suspected adverse reactions received electronically or by any other appropriate

means from patients and HCPs

According to current version GVP Module VI: • Medical confirmation should be sought for all patient reports

• MAHs should regularly screen internet/digital media (incl. website, blog, chat room, health portal, …) under their management/responsibility for potential reports of ADRs

• For reports from Patient Support Programmes : Solicited reports : e.g. MAH asks if adverse events were noted with use of product : MAH reports only when there is possible causal relationship as per reporter or MAH

Not-solicited reports : e.g. MAH contacts patient for a refill and is informed of a suspected adverse reaction : MAH should always report the case as this should be considered as a spontaneous report of suspected adverse reaction

Reporting Rules : Key changes (II)

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Literature monitoring :

Purpose : avoid duplicate reports in EudraVigilance

The EMA shall:

• Monitor selected medical literature for reports of suspected ADRs to medicinal products containing certain active substances

• Enter identified ICSRs into EudraVigilance

• Publish the list of active substances & medical literature

The MAH shall:

• Not be required to submit the suspected ADRs for medicinal products containing the active substances referred to in the list

• Monitor all other medical literature and report any ADRs

Timeline publication of list selected literature & substances: ??

Reporting Rules : Key changes (III)

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Reporting Rules : Key changes (III)Who to who? – rerouting process

To CAs To MAHs

Rerouting process

Source : S. Brosch (EMA) :Eudravigilance New Developments and Access toEudravigilance Data,

Second Stakeholders Forum dd.17 june 2012

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Good Vigilance Practice (DRAFT) (I) :Module VI : Management and reporting of adverse reactions to medicinal Products

Source : Gilles Touraille (EMA), Good Vigilance Practice : Module VI :Management and reporting of adverse reactions

to medicinal products, Stakeholders forum 27th February 2012

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Good Vigilance Practice (DRAFT) (II) : Module VI : Management and reporting of adverse reactions to medicinal Products

Source : Gilles Touraille (EMA), Good Vigilance Practice : Module VI :Management and reporting of adverse reactions

to medicinal products, Stakeholders forum 27th February 2012

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GVP Module VI: Structure Section A: Introduction

� Definitions relevant for the purpose of GVP VI applicable to Section B and C

Section B: Structures and Processes

� Agreed principles in relation to the collection, validation, management and reporting of suspected adverse reactions to MPs

Section C: Operation of EU Network

� EU specific requirements as defined in Reg. and Dir. in relation to suspected adverse reactions to authorized MPs for human use

� Requirements specific to NCAs in order to encourage reporting from HCPs, patients and consumers

� Requirements specific to MAHs in relation to MPs for which they hold ownership within or outside EU

Good Vigilance Practice (DRAFT) (III) : Module VI : Management and reporting of adverse reactions to medicinal Products

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Appendixes

• Detailed guidance on the monitoring of scientific and medical literature developed by the Agency

• Detailed guidance on the nullification of cases

• Business process maps and process descriptions in relation to :

� Identification of biological MPs

� Modalities for expedited reporting during interim and final arrangements,

� Transmission and rerouting to NCAs of ICSRs, transmission to WHO

� Data quality monitoring of ICSRs transmitted electronically, duplicate detection and management of ICSRs.

Good Vigilance Practice (DRAFT) (IV) :Module VI : Management and reporting of adverse reactions to medicinal Products

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International Standardisation (I) : general

ICH Steering Committee decision in 2006 collaborate with Standard Development Organisations (SDOs)

for development

of technical standards

At request of the

European

Commission, EMA is

stronlgy involved in

international

standardisation

activities

Dir 2010/84/EU Article 108:

“….use internationally agreed terminologies,

formats and standards for the conduct of

pharmacovigilance”

Proposed to use ISO formats & standards :

ISO ICSR 27953-2 : Individual Case Safety Report

5 ISO IDMP standards : Identification of Medicinal Products

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• The EMA to make public a format for the electronic

submission of information on medicinal products for human

use by 2 July 2011

• MAHs to electronically submit information to the EMA

electronically on all medicinal products for human use

authorised or registered in the EU, by 2 July 2012 at the

latest, using this format

• MAHs to inform the EMA of any new or varied marketing

authorisations granted in the EU using this format

International Standardisation (II) : art. 57(2) implementation

Stepwise ‘upgrade’ of the EudraVigilance Medicinal Product Dictionary (EVMPD): - Initial format: EudraVigilance Medicinal Product Report Message

- updated format by end of 2014 to be fully aligned with the 5 ISO

Identification of Medicinal Products (IDMP) standards

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• Description of the (invented) name• Description of the therapeutic area(s) e.g. ATC Code

• The designation of additional monitoring where applicable

• Description of the clinical particulars i.e. therapeutic indication(s)

• Details of the MAH

• Details of the marketing authorisation, including authorisation date, marketing status, Marketing authorisation procedure

• Country of marketing authorisation + MAH number

• Mutual-recognition procedure number/decentralised-procedure number

• Orphan drug designation

• Detailed description of the active substance(s), excipient(s),adjuvant(s) and their specific characteristics

• Description of the packaging information

• Electronic copy of the SPC, Package Leaflet

and annexes for CAPs)

International Standardisation (III) : art. 57(2) implementation

Information to be provided to EudraVigilance Medicinal Product Dictionary initially will include:

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International Standardisation (I) : art. 57(2) implementation…. BUT….

Concerns raised by MAHs : short timeline, high workload, availability of IT-tools, content (Structured

Substance Information), ….

EMA workshop with European pharmaceutical

industry associations (Jan 2012)

• Reduction of mandatory data compared to July 2011

description of packaging information

location of PhVSMF

regulated documents (condition of MA, PL)

• Structured Substance Information: not to be submitted until

agreement is reached

• SPC to be submitted for validation purposes

Stepwise approach to move forwards ISO IDMP

implementation as ultimate and longer term objective

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• Revised format published on 5 March 2012

• Significantly reduces the administrative burden and

helps MAHs to meet their legal deadline of

2 July 2012

International Standardisation (I) : art. 57(2) implementation…. BUT….

Link:www.ema.europa.eu :Home ��News and Events �� News and press release archive or http://eudravigilance.ema.europa.eu/human/index.asp

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Eudravigilance Data Access Policy (I)

Full access to EEA Competent Authorities of the Member States, to the Agency and the Commission

Partial Access to be implemented for HCPs, patients and consumers

•Data set for spontaneous reports

•Compliance with EU personal data protection legislation

Access for marketing authorisation holders planned as follows:•Data set for spontaneous reports

•Compliance with EU personal data protection legislation

•Access to EudraVigilance Data Warehouse and Analysis

•System (EVDAS) and data analysis and signal detection tools

•Results of EVDAS queries to be downloadable and printable either in aggregated format (e.g. as tabular or graphic presentations,line listings) or as individual report forms

•Downloads in ICH E2B format and in accordance with the ICH M2 message specifications

Access to research organisations planned

Source : Sabine Brosch, EudraVigilance New Developments and Access to EudraVigilance Data, Second Stakeholders

Forum on the implementation of the new legislation, 17 June 2011

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Eudravigilance Data Access Policy (II)

Source : Steven Lemeur (EMA), Implementation of the Eudravigilance Access Policy (Access to Eudravigilance data),

Thirth Stakeholders Forum on the implementation of the new legislation, 20 October 2011

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Eudravigilance Data Access Policy (III)



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Functionalities to support the operation of procedures that

ensure quality and integrity of the information collected in

EudraVigilance :

• Validation of ICSRs against defined business rules

• Duplicate detection and management

• Coding of product information

• ICSR data quality review

Eudravigilance Data Quality Management (I)

� Important for conduct of signal detection

and benefit risk assessment

� Ensure that accurate and reliable data

held in EudraVigilance are made available

(EudraVigilance Access Policy)

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Eudravigilance Data Quality Management (I)



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ThankThank youyou

for for youryour attentionattention

[email protected]@fagg.be

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Information related to ICSRs

Legislation :

• Directive 2010/84/EU : nationally authorised products

• Regulation (EU) No 1235/2010 : centrally authorised products

& EMA tasksLink : www.ema.europa.eu :Home ��Special Topics �� 2010 pharmacovigilance legislation

(Upper part)

Guidance :

Good pharmacovigilance practices (GVP) (DRAFT)Link : www.ema.europa.eu : Home ��Regulatory ��Human medicines �� Pharmacovigilance

�� 2010 pharmacovigilance legislation ��Good pharmacovigilance practices

EMA’s Stakeholder events : The EMA is hosting a series of stakeholder meetings during 2011 and 2012, aiming

to raise awareness of the requirements of the new legislation and promote the

exchange of ideas, concerns and opinions.Link : www.ema.europa.eu :Home ��Special Topics �� 2010 pharmacovigilance legislation

(lower part)

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Set of 5 ISO IDMP standards : final documents expected end 2012 :• ISO prEN 11615, Health Informatics, Identification of Medicinal Products (IDMP) standard ‘Data elements and structures for unique identification and exchange of regulated medicinal product information’

• ISO prEN 11616, Health Informatics, Identification of Medicinal Products (IDMP) standard ‘Data elements and structures for unique identification and exchange of regulated pharmaceutical product information’

ISO prEN 11238, Health Informatics, Identification of Medicinal Products (IDMP) standard ‘Data elements and structures for unique identification and exchange of regulated information on substances’

• ISO prEN 11239, Health Informatics, Identification of Medicinal Products (IDMP) standard ‘Data elements and structures for unique identification and exchange of regulated information on pharmaceutical dose forms, units of presentation, routes of administration and packaging’

• ISO prEN 11240, Health Informatics, Identification of Medicinal Products (IDMP) standard ‘Data elements and structures for unique identification and exchange of units of measurement’

ISO ICSR standard : final document : end 2011 :• ISO prEN 27953-2, Health Informatics ‘Individual Case Safety Reports’ for the electronic transmission of suspected adverse reactions

http://www.hl7.org/ �� Home �� Project Summary for IDMP Terminologies Project (JIC Project)

Information related to international standardisation

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